Therapeutic products can be administered to a human or animal in a variety of ways and the administration method is often matched to the specific requirements of the therapeutic product and its intended action. While oral administration is typically preferred, some therapeutic products, such as insulin, have to be administered in such as way as to avoid the digestive system, or it may be beneficial to deliver them directly to the site of intended action.
The administration of therapeutic products to avoid the digestive tract is known as parenteral delivery and is typically achieved by administering the therapeutic product as a liquid formulation directly into the circulation. This is commonly performed using a syringe or equivalent device to deliver a bolus of therapeutic product, or an infusion system capable of continuous, and in some cases programmed, delivery of therapeutic product. It is clear that the controlled administration of the therapeutic product more adequately matches the clinical requirement of these products, often offering better therapeutic control and reducing toxicity.
There is a growing demand for intensive insulin therapies for controlling glucose in people with diabetes. These therapies require that the patient administer regular insulin in an attempt to mimic the daily pattern of insulin release in an individual without diabetes. The pattern of insulin release in people without diabetes is complex. Generally, there is a background level of insulin that acts to control a fasting glucose and this is supplemented by temporary increases that counteract glucose released from ingested meals.
To meet this demand a number of infusion systems have appeared based on positive pressure reservoirs working in cooperation with a pulsatile pumping chamber having one-way check-valves operating at the inlet and/or the outlet of the pumping chamber.
An exemplary prior art infusion system is described in U.S. Pat. No. 4,486,190. This document describes an infusion system where therapeutic product is held in a reservoir at a positive pressure. Therapeutic product is withdrawn from the reservoir through a one-way check-valve that forms an inlet valve to a pumping chamber. A flow restrictor is provided at the outlet of the pumping chamber. Drawing of a membrane of the pumping chamber increases the volume of the pumping chamber, thereby decreasing the pressure in the pumping chamber. This causes an increase in the pressure differential across the inlet valve to beyond a predetermined activation pressure of the inlet valve which opens in response. This enables the therapeutic product to enter the pumping chamber. The pumping chamber membrane moves under the action of a solenoid which, when released, causes the pumping chamber membrane to return to its original position. The inlet valve shuts under the action of a return spring and the therapeutic product empties from the pumping chamber via the outlet and the flow restrictor. The system described in U.S. Pat. No. 4,486,190 suffers a drawback in that the filling efficiency of the pumping chamber is affected by the pressure at the outlet. In addition, the design of the system is prone to allowing uncontrolled flow of therapeutic product due to leaking of the inlet valve. To prevent this, the activation pressure of the inlet valve could be increased but this would then compromise the pumping efficiency.
U.S. Pat. No. 4,152,098 describes a micro-pump for an infusion system that incorporates one-way check-valves at an inlet and an outlet of the micro-pump. Each one-way check-valve is formed by sandwiching a rubber membrane between two rigid layers. The rigid layers have a protrusion formed on one layer and a corresponding recess formed in the opposite layer at the site of the valves. A fluid conduit passes up through a center of the protrusion that is covered by the membrane. The membrane has a hole offset from an opening of the fluid conduit in the protrusion. During assembly, the membrane is located onto one of the rigid layers and held in place by gluing it to one or both of the rigid layers. The gluing of the membrane to the rigid layer(s) ensures that the membrane does not move during assembly and stretches over the protrusion to provide sealing. The need to glue the membrane during the assembly process significantly increases the complexity of the manufacture of the micro-pump. It also serves to increase the opportunity for assembly problems and seepage of the glue. These problems are significantly increased when an attempt is made to reduce the size of micro-pumps yet further.
The provision of a one-way check-valve at the outlet of the pumping chamber having a sufficiently high activation pressure to prevent free flow of liquid under expected operating conditions is necessary for micro-pumps for use in infusion systems, where uncontrolled flow of therapeutic product into the patient would be unacceptable. The activation pressure of the outlet valve can be designed to be overcome by the pressure generated by a pumping stroke of the pumping chamber. On the other hand, the one-way check-valve at the inlet could have a relatively low activation pressure, sufficient to seal but which allows the inlet valve to open readily once a filling stroke of the pumping chamber initiates.
In the above described prior art, the valves are assembled using conventional machining techniques and are relatively large. In addition, the devices described are not suitable for disposable, short term use.
WO 02/068823 describes a further passive membrane-type micro-valve formed of multiple layers having cut outs. The assembled valve includes a membrane having an aperture formed therein. A valve inlet is disposed on one side of the membrane and a valve outlet is disposed on the opposite side. A region of the membrane immediately surrounding the aperture is stretched over a valve seat on which the membrane rests when the valve is closed. Again, a positive fluid pressure in the valve inlet causes the membrane to deflect from the valve seat when above some undefined activation pressure, and fluid is then able to pass through the small aperture and from the valve outlet. A reduction in the fluid pressure permits the membrane to return to the valve seat, closing the valve. Valves of this type are slightly improved over those in U.S. Pat. No. 4,152,098 since some consideration is given to factors affecting the activation pressure. However, the membrane material is inherently flexible giving rise to misalignment of the inlet, outlet and valve seat during manufacture. This can adversely affect control of the activation pressure. It is also observed in this type of valve design that the tension of the valve membrane cannot be accurately controlled during the assembly of the device and that this leads to variability in the performance of the valve.
There is therefore a need in the art for an improved one-way micro-valve for a micro-pump, that is very small, lightweight, inexpensive and disposable, having an accurately defined activation pressure. The micro-valve should also be suitable for manufacture in a variety of sizes for various applications and having a range of accurately predetermined activation pressures. These and other objects will become apparent from the following description of the invention.